The primary aim of this research is to ascertain by peptide synthesis the precise amino acid sequence(s) conferring on the guinea pig basic protein (BP) molecule the unique capacity to induce hyperactive experimental allergic encephalomyelitis (EAE). Initially, the minimal chemical requirements for induction of both ordeinary and hyperacute EAE will be defined by comparing the encephalitogenic activity of peptides synthesized according to the known sequences of guinea pig and rat BPs. Once the immunogenic determinant(s) of guinea pig BP involved in hyperacture EAE (HEAE) induction is (are) identified, the contribution of each amino acid within the determinants(s) will be evaluated by analog synthesis. The guinea pig peptides will be examined singly, in combination and conjugated to determine whether the hyperacute encephalitogenicity is due to synergy of separate encephalitogenic determinants or whether a second determinant is acting as a nonencephalitogenic carrier, perhaps preferentially inducing helper T-lymphocytes to direct IgE secreting B cells. BIBLIOGRAPHIC REFERENCES: Westall, F. C., Thompson, M., and Robinson, A. B. Degradation of encephalitogenic protein in aerobic ascorbic acid solutions. Exper., 32, 848-849 (1976). Lennon, V. A., Westall, F. C., Thompson, M., and Ward, E. Antigen, host, and adjuvant requirements for induction of hyperacute EAE. Eur. J. Immunol., 6, 805-810 (1976).